Trial Outcomes & Findings for A Study of Duloxetine (LY248686) in Participants With Chronic Osteoarthritis and Knee Pain in Japan (NCT NCT02248480)

Last Updated: 2019-09-26

Results Overview

Brief Pain Inventory Severity: Average Pain Score: A self-reported scale that measures the severity of pain based on the average pain experienced during the past 24-hours. The severity scores ranged from 0 (no pain) to 10 (pain as severe as you can imagine). Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach including administration groups, observation points, and interaction between the administration groups and observation points as fixed effects, and BPI average pain severity at baseline as covariates.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

354 participants

Primary outcome timeframe

Baseline, Week 14

Results posted on

2019-09-26

Participant Flow

All started participants (pt) were randomized and received at least one dose of study drug. Efficacy population had at least 1 post-dose efficacy assessment.

Participant milestones

Participant milestones
Measure	Duloxetine Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 12 weeks administered orally once daily. Tapering week doses of 40 mg for three days and 20 mg for four days.	Placebo Placebo administered orally once a day for 15 weeks.
Overall Study STARTED	178	176
Overall Study Efficacy Population	177	176
Overall Study COMPLETED	161	162
Overall Study NOT COMPLETED	17	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Duloxetine Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 12 weeks administered orally once daily. Tapering week doses of 40 mg for three days and 20 mg for four days.	Placebo Placebo administered orally once a day for 15 weeks.
Overall Study Lack of Efficacy	4	6
Overall Study Adverse Event	11	2
Overall Study Withdrawal by Subject	2	4
Overall Study Entry Criteria Not Met	0	1
Overall Study Other:Physician Decision	0	1

Baseline Characteristics

A Study of Duloxetine (LY248686) in Participants With Chronic Osteoarthritis and Knee Pain in Japan

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Duloxetine n=177 Participants Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 12 weeks administered orally once daily. Tapering week doses of 40 mg for three days and 20 mg for four days.	Placebo n=176 Participants Placebo administered orally once a day for 15 weeks.	Total n=353 Participants Total of all reporting groups
Age, Continuous	65.5 years STANDARD_DEVIATION 8.0 • n=5 Participants	66.4 years STANDARD_DEVIATION 8.4 • n=7 Participants	65.9 years STANDARD_DEVIATION 8.2 • n=5 Participants
Sex: Female, Male Female	142 Participants n=5 Participants	132 Participants n=7 Participants	274 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	44 Participants n=7 Participants	79 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	177 Participants n=5 Participants	176 Participants n=7 Participants	353 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Japan	177 participants n=5 Participants	176 participants n=7 Participants	353 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 14

Population: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment.

Outcome measures

Outcome measures
Measure	Duloxetine n=177 Participants Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 12 weeks administered orally once daily. Tapering week doses of 40 mg for three days and 20 mg for four days.	Placebo n=176 Participants Placebo administered orally once a day for 15 weeks.
Change From Baseline on the Brief Pain Inventory (BPI) 24-Hour Average Pain Score	-2.57 units on a scale Standard Error 0.12	-1.80 units on a scale Standard Error 0.12

SECONDARY outcome

Timeframe: Baseline, 14 Weeks

Population: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment.

Patient's Global Impressions of Improvement Scale: PGI-I measures a participant's perception of improvement at the time of assessment compared with the start of treatment. Score ranges from 1 (very much better) to 7 (very much worse). Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach including administration groups, observation points, and interaction between the administration groups and observation points as fixed effects, and PGI-severity at baseline as covariates.

Outcome measures

Outcome measures
Measure	Duloxetine n=177 Participants Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 12 weeks administered orally once daily. Tapering week doses of 40 mg for three days and 20 mg for four days.	Placebo n=176 Participants Placebo administered orally once a day for 15 weeks.
Change From Baseline in Patient Global Impression of Improvement (PGI-Improvement)	2.23 units on a scale Standard Error 0.09	2.84 units on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment.

CSI-S measures severity of illness at the time of assessment compared with start of treatment with scores ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach including administration groups, observation points, and interaction between the administration groups and observation points as fixed effects, and baseline data as covariates.

Outcome measures

Outcome measures
Measure	Duloxetine n=177 Participants Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 12 weeks administered orally once daily. Tapering week doses of 40 mg for three days and 20 mg for four days.	Placebo n=176 Participants Placebo administered orally once a day for 15 weeks.
Change From Baseline on the Clinical Global Impression of Severity (CGI-S)	-1.71 units on a scale Standard Error 0.07	-1.22 units on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: All participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment. The last observation carried forward (LOCF) was used.

36-item Short-Form Health Survey: SF-36 Health Status Survey is a generic, health-related scale assessing participant's quality of life on 8 domains: physical functioning, social functioning, bodily pain, vitality, mental health, role-physical, role-emotional and general health. Domain scores: general health (range: 5-25); physical functioning (range: 10-30); role-physical (range: 4-8); role-emotional (range: 3-15); social functioning (range: 2-10); bodily pain (range: 2-12); vitality (range: 4-20); mental health (range: 5-25). Each raw scale score was converted to a scale score ranging from 0-100 points, , with higher values representing a better outcome \[(Raw score) - min{raw score}\] / (max {raw score} - min{raw score}) x 100\]. Least squares (LS) mean was calculated using Analysis of covariance (ANCOVA) approach including administration groups as fixed effects, and baseline data as covariate.

Outcome measures

Outcome measures
Measure	Duloxetine n=177 Participants Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 12 weeks administered orally once daily. Tapering week doses of 40 mg for three days and 20 mg for four days.	Placebo n=176 Participants Placebo administered orally once a day for 15 weeks.
Change From Baseline on the 36-Item Short-Form Health Survey (SF-36) Physical Functioning	12.62 units on a scale Standard Error 1.27	6.23 units on a scale Standard Error 1.27
Change From Baseline on the 36-Item Short-Form Health Survey (SF-36) Role (Physical)	11.44 units on a scale Standard Error 1.29	3.66 units on a scale Standard Error 1.30
Change From Baseline on the 36-Item Short-Form Health Survey (SF-36) Bodily Pain	16.32 units on a scale Standard Error 1.22	9.63 units on a scale Standard Error 1.22
Change From Baseline on the 36-Item Short-Form Health Survey (SF-36) General Health	5.58 units on a scale Standard Error 0.93	1.82 units on a scale Standard Error 0.94
Change From Baseline on the 36-Item Short-Form Health Survey (SF-36) Vitality	3.99 units on a scale Standard Error 1.04	3.16 units on a scale Standard Error 1.04
Change From Baseline on the 36-Item Short-Form Health Survey (SF-36) Social Functioning	5.66 units on a scale Standard Error 1.14	2.54 units on a scale Standard Error 1.15
Change From Baseline on the 36-Item Short-Form Health Survey (SF-36) Role (Emotional)	6.32 units on a scale Standard Error 1.27	0.70 units on a scale Standard Error 1.28
Change From Baseline on the 36-Item Short-Form Health Survey (SF-36) Mental Health	3.02 units on a scale Standard Error 0.99	1.48 units on a scale Standard Error 0.99

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment. The last observation carried forward (LOCF) was used.

Beck Depression Inventory-II: BDI-II is a 21-item, participant-completed questionnaire to assess characteristics of depression. Each of the 21 items corresponding to symptoms of depression were scored on a 4-point scale ranging from 0 to 3 and was summed to give a single score. A total score of 0-13 was considered minimal range, 14-19 was mild, 20-28 was moderate, and 29-63 was severe. Least squares (LS) mean was calculated using a ANCOVA approach' including administration groups as fixed effects, and baseline data as covariate.

Outcome measures

Outcome measures
Measure	Duloxetine n=177 Participants Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 12 weeks administered orally once daily. Tapering week doses of 40 mg for three days and 20 mg for four days.	Placebo n=176 Participants Placebo administered orally once a day for 15 weeks.
Change From Baseline on the Beck Depression Inventory (BDI-II) Total Score	-0.78 units on a scale Standard Error 0.23	-0.51 units on a scale Standard Error 0.24

SECONDARY outcome

Timeframe: Baseline through Week 14

Population: All randomized participants who received at least 1 dose of study drug.

Participants evaluated their experience with and details of falls which were recorded.

Outcome measures

Outcome measures
Measure	Duloxetine n=178 Participants Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 12 weeks administered orally once daily. Tapering week doses of 40 mg for three days and 20 mg for four days.	Placebo n=176 Participants Placebo administered orally once a day for 15 weeks.
Percentage of Participants With Fall Events From Fall Questionnaire	10.1 percentage of participants	9.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment.

The 24-question WOMAC Osteoarthritis Index assesses osteoarthritis symptoms using pain (5 questions), stiffness (2 questions) and physical function (17 questions) subscales. The WOMAC Osteoarthritis Index version 3.1 was administered according to the study schedule. The WOMAC total score was calculated for each participant at each time point for analysis as the mean total score, range 0 (none) -96 (extreme). Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach including administration groups, observation points, and interaction between the administration groups and observation points as fixed effects, and baseline data as covariates.

Outcome measures

Outcome measures
Measure	Duloxetine n=177 Participants Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 12 weeks administered orally once daily. Tapering week doses of 40 mg for three days and 20 mg for four days.	Placebo n=176 Participants Placebo administered orally once a day for 15 weeks.
Change From Baseline on the Western Ontario and McMaster Osteoarthritis Index (WOMAC) Questionnaire Total Score	-17.41 units on a scale Standard Error 0.91	-10.45 units on a scale Standard Error 0.91

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: Zero participants analyzed. PGAI outcome measure was registered incorrectly thus no analysis produced.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment. The last observation carried forward (LOCF) was used.

The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument and was completed on five dimensions (mobility, self care, usual activities, pain/discomfort and anxiety/depression) to measure health-related quality of life on a scale from 0-1, with the higher score indicating a better health state perceived by the participant. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a three level scale (no problem, some problems, and major problems). These combinations of attributes were converted into a weighted health-state Index Score according to the Japan population-based algorithm. Least squares (LS) mean was calculated using an ANCOVA approach including administration groups as fixed effects, and baseline data as covariate.

Outcome measures

Outcome measures
Measure	Duloxetine n=177 Participants Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 12 weeks administered orally once daily. Tapering week doses of 40 mg for three days and 20 mg for four days.	Placebo n=176 Participants Placebo administered orally once a day for 15 weeks.
Change From Baseline on the 5 Dimension (EQ-5D) Version of the European Quality of Life Instrument	0.12 units on a scale Standard Error 0.01	0.07 units on a scale Standard Error 0.01

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment.

BPI-S and BPI-I are self-reported scales measuring severity of pain and interference on function. Severity scores: 0 (no pain) to 10 (severe pain) on each question assessing worst pain, least pain, and average pain in past 24 hours, and pain right now. Interference scores: 0 (does not interfere) to 10 (completely interferes) on each question assessing interference of pain in past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Average interference = average of non-missing scores of individual interference items. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach including administration groups, observation points, and interaction between the administration groups and observation points as fixed effects, and baseline data as covariates.

Outcome measures

Outcome measures
Measure	Duloxetine n=177 Participants Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 12 weeks administered orally once daily. Tapering week doses of 40 mg for three days and 20 mg for four days.	Placebo n=176 Participants Placebo administered orally once a day for 15 weeks.
Change in Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S, BPI-I) Change From Baseline in BPI Pain Severity Items and Interference Items Score Worse Pain	-2.92 units on a scale Standard Error 0.15	-2.13 units on a scale Standard Error 0.15
Change in Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S, BPI-I) Change From Baseline in BPI Pain Severity Items and Interference Items Score Least Pain	-1.61 units on a scale Standard Error 0.11	-1.05 units on a scale Standard Error 0.11
Change in Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S, BPI-I) Change From Baseline in BPI Pain Severity Items and Interference Items Score Pain Right Now	-2.29 units on a scale Standard Error 0.13	-1.52 units on a scale Standard Error 0.13
Change in Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S, BPI-I) Change From Baseline in BPI Pain Severity Items and Interference Items Score General Activity	-2.42 units on a scale Standard Error 0.14	-1.52 units on a scale Standard Error 0.14
Change in Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S, BPI-I) Change From Baseline in BPI Pain Severity Items and Interference Items Score Walking Ability	-2.58 units on a scale Standard Error 0.14	-1.74 units on a scale Standard Error 0.14
Change in Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S, BPI-I) Change From Baseline in BPI Pain Severity Items and Interference Items Score Mood	-1.95 units on a scale Standard Error 0.12	-1.43 units on a scale Standard Error 0.12
Change in Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S, BPI-I) Change From Baseline in BPI Pain Severity Items and Interference Items Score Normal Work	-2.48 units on a scale Standard Error 0.13	-1.67 units on a scale Standard Error 0.13
Change in Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S, BPI-I) Change From Baseline in BPI Pain Severity Items and Interference Items Score Relationship to People	-1.23 units on a scale Standard Error 0.11	-0.81 units on a scale Standard Error 0.11
Change in Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S, BPI-I) Change From Baseline in BPI Pain Severity Items and Interference Items Score Sleep	-1.65 units on a scale Standard Error 0.11	-1.19 units on a scale Standard Error 0.11
Change in Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S, BPI-I) Change From Baseline in BPI Pain Severity Items and Interference Items Score Enjoyment of Life	-1.78 units on a scale Standard Error 0.12	-1.16 units on a scale Standard Error 0.12
Change in Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S, BPI-I) Change From Baseline in BPI Pain Severity Items and Interference Items Score Average of 7 Items	-2.01 units on a scale Standard Error 0.11	-1.34 units on a scale Standard Error 0.11

SECONDARY outcome

Timeframe: Baseline,Week 14

Population: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment. The last observation carried forward (LOCF) was used.

Outcome measures

Outcome measures
Measure	Duloxetine n=177 Participants Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 12 weeks administered orally once daily. Tapering week doses of 40 mg for three days and 20 mg for four days.	Placebo n=176 Participants Placebo administered orally once a day for 15 weeks.
Percentage of Participants With a 30% and 50% Reduction in Average Pain Score on Weekly Mean of the 24-Hour Average Pain Score on the 11-Point Numeric Rating Scale >=30%	72.3 percentage of participants	52.8 percentage of participants
Percentage of Participants With a 30% and 50% Reduction in Average Pain Score on Weekly Mean of the 24-Hour Average Pain Score on the 11-Point Numeric Rating Scale >=50%	55.4 percentage of participants	38.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment.

24-hour average pain severity scores were recorded daily on an 11-point Likert scale, an ordinal scale, with scores ranging from 0 (no pain) to 10 (worst possible pain). The 11-point Likert scale was also used for assessment of average pain and worst pain within 24-hours. Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach including administration groups, observation points, and interaction between the administration groups and observation points as fixed effects, and baseline data as covariates.

Outcome measures

Outcome measures
Measure	Duloxetine n=177 Participants Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 12 weeks administered orally once daily. Tapering week doses of 40 mg for three days and 20 mg for four days.	Placebo n=176 Participants Placebo administered orally once a day for 15 weeks.
Change From Baseline on Weekly Mean of the 24-Hour Average Pain and Worst Pain Score Average Pain	-2.45 units on a scale Standard Error 0.12	-1.79 units on a scale Standard Error 0.12
Change From Baseline on Weekly Mean of the 24-Hour Average Pain and Worst Pain Score Worst Pain	-2.73 units on a scale Standard Error 0.14	-1.97 units on a scale Standard Error 0.14

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment. The last observation carried forward (LOCF) was used.

Outcome measures

Outcome measures
Measure	Duloxetine n=177 Participants Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 12 weeks administered orally once daily. Tapering week doses of 40 mg for three days and 20 mg for four days.	Placebo n=176 Participants Placebo administered orally once a day for 15 weeks.
Percentage of Participants With Reduction of ≥30% and ≥50% in BPI Average Pain Score >=30%	72.3 percentage of participants	52.8 percentage of participants
Percentage of Participants With Reduction of ≥30% and ≥50% in BPI Average Pain Score >=50%	55.4 percentage of participants	38.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment. The last observation carried forward (LOCF) was used.

A responder is required to meet at least one condition: reduction of ≥50% and ≥2 score in Weekly Mean of the 24-Hour Average Pain Score, reduction of ≥50% or ≥13.6 score in WOMAC (difficulty in dairy activity) and meet ≥2 out of following 3 conditions: reduction of ≥20% and ≥1 score in Weekly Mean of the 24-Hour Average Pain, reduction of ≥20% and ≥6.8 score in WOMAC (difficulty in dairy activity), PGAI score ≥2.

Outcome measures

Outcome measures
Measure	Duloxetine n=177 Participants Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 12 weeks administered orally once daily. Tapering week doses of 40 mg for three days and 20 mg for four days.	Placebo n=176 Participants Placebo administered orally once a day for 15 weeks.
Percentage of Participants With a Responder Rate Based on OMERACT-OARSI Criteria	83.6 percentage of participants	61.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 14 Weeks

Population: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment.

The WOMAC index (pain, stiffness, physical function subscales) was completed by the participant.The pain subscale had 5 questions on pain associated with every day tasks. Each question was answered using a 5-point Likert scale (0 to 4). The pain subscale has a range of scores of 0 (none) to 20 (extreme). Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach including administration groups, observation points, and interaction between the administration groups and observation points as fixed effects, baseline data as covariates.

Outcome measures

Outcome measures
Measure	Duloxetine n=177 Participants Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 12 weeks administered orally once daily. Tapering week doses of 40 mg for three days and 20 mg for four days.	Placebo n=176 Participants Placebo administered orally once a day for 15 weeks.
Change From Baseline on the WOMAC Questionnaire Pain Subscale	-3.99 units on a scale Standard Error 0.21	-2.43 units on a scale Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline, 14 Weeks

Population: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment.

The WOMAC index (pain, stiffness, physical function subscales) will be completed by the participant.The stiffness subscale had 2 questions on stiffness associated with time of day (morning versus later in the day). Each question was answered using a 5-point Likert scale (0 to 4). The stiffness subscale has a range of scores of 0 (none) to 8 (extreme). Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach including administration groups, observation points, and interaction between the administration groups and observation points as fixed effects, baseline data as covariates.

Outcome measures

Outcome measures
Measure	Duloxetine n=177 Participants Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 12 weeks administered orally once daily. Tapering week doses of 40 mg for three days and 20 mg for four days.	Placebo n=176 Participants Placebo administered orally once a day for 15 weeks.
Change From Baseline on the WOMAC Questionnaire Stiffness Subscale	-1.66 units on a scale Standard Error 0.09	-0.98 units on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: Baseline, 14 Weeks

Population: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment.

The WOMAC osteoarthritis scale consists of 24 items in 3 subscales: pain, stiffness, and physical function. The physical function subscale rates participant pain during stair use, rising from sitting, standing, bending, walking, getting in/out of a car, shopping, putting on/taking off socks, rising from bed, lying in bed, getting in/out of the bath, sitting, getting on/off the toilet, heavy household duties, and light household duties. Each question was answered using a 5-point Likert scale (0 to 4). Physical Function Subscale has a range of scores of 0 (none) to 68 (extreme). Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach including administration groups, observation points, and interaction between the administration groups and observation points as fixed effects, baseline data as covariates.

Outcome measures

Outcome measures
Measure	Duloxetine n=177 Participants Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 12 weeks administered orally once daily. Tapering week doses of 40 mg for three days and 20 mg for four days.	Placebo n=176 Participants Placebo administered orally once a day for 15 weeks.
Change From Baseline on the WOMAC Questionnaire Physical Function Subscale	-11.77 units on a scale Standard Error 0.67	-7.07 units on a scale Standard Error 0.66

Adverse Events

Duloxetine

Serious events: 1 serious events

Other events: 120 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 98 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Duloxetine n=178 participants at risk Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 12 weeks administered orally once daily. Tapering week doses of 40 mg for three days and 20 mg for four days.	Placebo n=176 participants at risk Placebo administered orally once a day for 15 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cerebellar tumour	0.00% 0/178 All randomized participants who received at least 1 dose of study drug.	0.57% 1/176 • Number of events 1 All randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant ascites	0.56% 1/178 • Number of events 1 All randomized participants who received at least 1 dose of study drug.	0.00% 0/176 All randomized participants who received at least 1 dose of study drug.

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60